Improvements for performing and facilitating the recovery after hematopoietic stem cell transplantation

Abstract

A method enhances hematopoietic reconstitution and recovery after hematopoietic stem cell transplantation, which is based on the administration of estetrol to the subject that has undergone the transplantation, because estetrol induced an increment in the percentage of hematopoietic cells derived from transplanted donor cells in the recipient. Additionally, estetrol increases the donor contribution in the hematopoietic stem cell compartment. A method also increases the number of hematopoietic progenitor or stem cells in a culture, based as well in the addition of estetrol to the culture. As the obtained hematopoietic progenitor or stem cells can also be transplanted, the method increases the availability of donor cells for transplantation. Thus, hematopoietic stem cell transplantation is improved in patients.

1 . An estrogen comprising estetrol for enhancing hematopoietic reconstitution after hematopoietic stem cell transplantation (HSCT) or hematopoietic progenitor cell transplantation in a subject wherein the estrogen is configured and arranged to be administered in an effective amount to the subject recipient of the transplantation. 
     
     
         2 . The estrogen according to  claim 1 , wherein the estrogen is administered systemically. 
     
     
         3 . The estrogen according to  claim 1 , wherein the estrogen is administered after the transplantation of hematapoietic stem cells or progenitor stem cells. 
     
     
         4 . A method for increasing the number of hematopoietic progenitor cells and/or hematopoietic stem cells in a culture, the method comprising the steps of:
 adding an estrogen to the cell culture with the hematopoietic progenitor cells and/or the hematopoietic stem cells,   culturing the cells in the presence of the estrogen,   collecting the hematopoietic progenitor cells and/or the hematopoietic stem cells,   wherein the estrogen added to the cell culture is estetrol.   
     
     
         5 . The method according to  claim 4 , comprising culturing the cells in the presence of a niche of bone marrow-mesenchymal stem cells (BM-MSCs). 
     
     
         6 . The method according to  claim 4 , comprising culturing the cells in the presence of the estrogen during at least a week. 
     
     
         7 . A hematopoietic progenitor cell or an hematopoietic stem cell or a composition comprising hematopoietic progenitor cells and/or hematopoietic stem cells for transplantation to a subject, wherein the cell or cells has(have) been cultured in the presence of an estrogen which is estetrol. 
     
     
         8 . The hematopoietic progenitor cell or the hematopoietic stem cell or a population of hematopoietic progenitor cells and/or hematopoietic stem cells according to  claim 7 , wherein the hematopoietic progenitor cell or the hematopoietic stem cell or population of hematopoietic progenitor cells and/or hematopoietic stem cells have been obtained by applying a method comprising the steps of:
 adding the estetrol to the cell culture with the hematopoietic progenitor cells and/or the hematopoietic stem cells;   culturing the cells in the presence of the estetrol;   collecting the hematopoietic progenitor cells and/or the hematopoietic stem cells   
     
     
         9 . The estrogen according to  claim 1 , wherein the transplanted hematopoietic progenitor cells and/or hematopoietic stem cells are autologous or allogenic to the subject. 
     
     
         10 . The estrogen according to  claim 1 , wherein the subject is a human being. 
     
     
         11 . The estrogen according to  claim 1 , wherein the subject suffers or has suffered from a disease which is selected from the group of: solid tumor, myeloma, lymphoma any blood disease requiring HSC transplantation after bone marrow ablation or myelosuppression by chemo- and/or radio-therapy, anemia, primary or acquired immunodeficiency, an inherited genetic disease that can be cured by allogeneic hematopoietic progenitors transplantation, an inherited genetic disease that can be cured by transplantation of genetically corrected hematopoietic progenitors. 
     
     
         12 . The estrogen according to  claim 1 , wherein the subject is a candidate for bone marrow or stem cell transplantation, or a subject that has received bone marrow after ablating chemo- or radio-therapy. 
     
     
         13 . The estrogen according to  claim 1 , wherein the hematopoietic progenitor cells or the hematopoietic stem cells transplanted or to be transplanted are obtained from peripheral blood, cord blood, bone marrow, amniotic fluid, placental cord or any other hematopoietic cell source. 
     
     
         14 . The hematopoietic progenitor cell or the hematopoietic stem cell or the population of hematopoietic progenitor cells and/or hematopoietic stem cells according to  claim 7 , wherein the transplanted hematopoietic progenitor cells and/or the hematopoietic stem cells are autologous or allogenic to the subject. 
     
     
         15 . The hematopoietic progenitor cell or the hematopoietic stem cell or the population of hematopoietic progenitor cells and/or hematopoietic stem cells according to  claim 7 , wherein the subject is a human being. 
     
     
         16 . The hematopoietic progenitor cell or the hematopoietic stem cell or the population of hematopoietic progenitor cells and/or hematopoietic stem cells according to  claim 7 , wherein the subject suffers or has suffered from a disease which is selected from the group of: solid tumor, myeloma, lymphoma any blood disease requiring HSC transplantation after bone marrow ablation or myelosuppression by chemo- and/or radio-therapy, anemia, primary or acquired immunodeficiency, an inherited genetic disease that can be cured by allogeneic hematopoietic progenitors transplantation, an inherited genetic disease that can be cured by transplantation of genetically corrected hematopoietic progenitors. 
     
     
         17 . The hematopoietic progenitor cell or the hematopoietic stem cell or the population of hematopoietic progenitor cells and/or hematopoietic stem cells according to  claim 7 , wherein the subject is a candidate for bone marrow or stem cell transplantation, or a subject that has received bone marrow after ablating chemo-therapy or radio-therapy. 
     
     
         18 . The method according to  claim 4 , wherein the hematopoietic progenitor cells or the hematopoietic stem cells transplanted or to be transplanted are obtained from peripheral blood, cord blood, bone marrow, amniotic fluid, placental cord or any other hematopoietic cell source. 
     
     
         19 . The hematopoietic progenitor cell or the hematopoietic stem cell or the population of hematopoietic progenitor cells and/or hematopoietic stem cells according to  claim 7 , wherein the hematopoietic progenitor cells or the hematopoietic stem cells transplanted or to be transplanted are obtained from peripheral blood, cord blood, bone marrow, amniotic fluid, placental cord or any other hematopoietic cell source.